Robson Fran, Khan Khadija Shahed, Le Thi Khanh, Paris Clément, Demirbag Sinem, Barfuss Peter, Rocchi Palma, Ng Wai-Lung
School of Biological Sciences, University of Bristol, Bristol, UK.
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
Mol Cell. 2020 Sep 3;79(5):710-727. doi: 10.1016/j.molcel.2020.07.027. Epub 2020 Aug 4.
The coronavirus disease 2019 (COVID-19) that is wreaking havoc on worldwide public health and economies has heightened awareness about the lack of effective antiviral treatments for human coronaviruses (CoVs). Many current antivirals, notably nucleoside analogs (NAs), exert their effect by incorporation into viral genomes and subsequent disruption of viral replication and fidelity. The development of anti-CoV drugs has long been hindered by the capacity of CoVs to proofread and remove mismatched nucleotides during genome replication and transcription. Here, we review the molecular basis of the CoV proofreading complex and evaluate its potential as a drug target. We also consider existing nucleoside analogs and novel genomic techniques as potential anti-CoV therapeutics that could be used individually or in combination to target the proofreading mechanism.
2019年冠状病毒病（COVID-19）正在全球范围内对公共卫生和经济造成严重破坏，这提高了人们对人类冠状病毒（CoV）缺乏有效抗病毒治疗方法的认识。许多当前的抗病毒药物，特别是核苷类似物（NA），通过掺入病毒基因组并随后破坏病毒复制和保真度来发挥作用。长期以来，CoV在基因组复制和转录过程中校对和去除错配核苷酸的能力一直阻碍着抗CoV药物的开发。在这里，我们综述了CoV校对复合物的分子基础，并评估了其作为药物靶点的潜力。我们还将现有的核苷类似物和新型基因组技术视为潜在的抗CoV治疗方法，这些方法可以单独使用或联合使用来靶向校对机制。
